Nonhuman primates are instrumental in research involving Category A-C biodefense pathogens. Cynomolgus macaques (M. Fascicularis) are particularly desireable because they are comparitively inexpensive and widely available. However, little is known about the immunogenetics ot Cynomolgus macaques, complicating the evaluation of pathogen-specific cellular immune responses. in Specific Aim 1: Wewill identify at least 60 Major Histocompatibility Complex (MHC) class I and 50 MHC class II molecules expressed by Cynomolgus macaques and develop methods for high-throughput ge- notyping for these alleles. MHC class I and class II alleles may vary among Cynomolgus macaques obtained from different countries, so we will examine the immunogenetics of animals from China, Mauritius, Vietnam, Indonesia, and the Phillipines. More than 12,000 Cynomolgus macaques were imported from these countries in FY2003. In Specific Aim 2, we will develop preliminary peptide binding motifs for 10common MHC class I and 10 common MHC class II alleles identified in Specific Aim 1. If Cynomolgus macaques from different regions have distinct MHC allele repertoires, we will focus on the definition of peptide binding motifs for alleies found in Chinese, Mauritian, and Vietnamese macaques. More than 75% of the Cynomolgus macaques imported into the United States in FY2003 were brought from one of these countries. The strengths of experienced molecular immunogeneticists and protein biochemists a-e combined in this proposal, enabling the high-throughput characterization of Cynomolgus macaque major histocompatibility complex (MHC) molecules and the pathogen-derived peptides that bind to them. These studies will facilitate the development of species-specific reagents (such as MHC: peptide tetramers) that expand the utility of Cynomolgus macaques in preclinical vaccine trials and studies of disease pathogenesis.